PROJECT SUMMARY The overall goal of this proposal is to examine the role of emotion regulation (ER) in sleep bruxism (SB). SB is characterized by extreme levels of masticatory muscle activity (MMA) during sleep, expressed as teeth grinding or clenching. SB may proximally lead to tooth damage, orofacial pain, and impaired sleep; predispose to the development of joint degenerative disorders; and ultimately present a preclinical sign for a broader range of neurodegenerative disorders. However, there is as yet no curative treatment for SB, and the mechanisms underlying SB are not well understood. To fill this gap, we propose an integrative neurobiological framework that focuses on the involvement of impaired downregulation of wake-time emotion in SB. We will test basic tenets of this framework by addressing four major aims: Aim 1 tests differences in task-related neural activation during ER in individuals with SB (SB+) vs. matched controls (SB?). Aim 2 investigates direct and indirect pathways associating task- related prefrontal cortex activatin during ER with MMA during sleep among SB+ and SB?. Aim 3 examines whether neural activation during ER can be experimentally manipulated in SB+. Aim 4 addresses causal mechanisms by investigating whether more efficient task-related prefrontal cortex activation during ER decreases MMA during sleep in SB+ through decreased task-related emotional activation of the amygdala. 100 SB+ and 50 SB? will be defined based on polysomnographic research diagnostic criteria. Functional activations of brain regions of interest during an ER task will be assessed and ambulatory monitoring of MMA during sleep will be conducted. In SB+, ER will be experimentally manipulated and effects will be assessed on functional activations of brain regions of interest during the ER task as well as on MMA during sleep. The proposed work is part of a programatic translational research agenda to develop novel effective therapies that target ER processes to alleviate affective, sleep, and stress-induced neurodegenerative disorders.